Human epidermis is composed of, from deep to superficial, stratum basale, stratum spinosum, stratum granulosum, and stratum corneum. In normal human skin, the stratum corneum has a barrier function to protect skin from physical and chemical stimulation.
In normal skin, cell turnover generally occurs in a 28-day cycle. In normal skin cell turnover, keratinocytes are pushed upward from the stratum granulosum to the stratum corneum. At this time, keratinocytes are differentiated and enucleated to cause a loss of nucleated cells, forming a mature stratum corneum. However, when, for example, cell turnover occurs in an overly rapid manner, enucleation does not occur in the final stage of keratinocyte differentiation, and the stratum corneum is thereby put in the condition of parakeratosis, causing a significant decrease in the skin barrier function. Application of oleic acid to skin also causes the same condition as parakeratosis (Non-Patent Document 1).
Epimorphin is considered to be one of the factors involved in regulation of epithelial morphogenesis (Non-Patent Documents 2 to 5). There has also been a report that in epimorphin knockout mice, the induction of malignant transformation is decreased (see, for example, Non-Patent Document 6).
In order to regulate epithelial morphogenesis, oligopeptides, which inhibit the epithelial morphogenesis-promoting activity of epimorphin, have been suggested (see, for example, Patent Documents 1 and 2).
However, the inhibitory action of oligopeptides on the epithelial morphogenesis-promoting activity is not sufficient to regulate epithelial morphogenesis. Therefore, there has been a demand for a more useful compound that can inhibit with high efficiency, for example, the occurrence of abnormal morphology and abnormal differentiation of epithelial cells of skin, etc., induced by epimorphin.